[unreadable] The nucleus accumbens (NAc) is an important neural structure involved in mediating the reinforcing actions of natural rewards as well as drugs of abuse, such as cocaine. Indeed, individual populations of NAc cells selectively encode for cocaine or natural rewards. However, experiences with powerful rewards impact behavioral reactions to lesser rewards and ultimately, natural rewards are devalued as they are compared to drugs of abuse. In fact, dysfunctional reward comparison behavior is a sufficient criterion for the diagnosis of Substance Abuse as defined by the DSM-IV, and one of the criteria for the diagnosis of Substance Dependence. Unfortunately, the neural foundation of the pathological interaction of drugs of abuse and natural rewards remains unclear. The PI will investigate these interactions in real time using electrophysiological and electrochemical recordings in the NAc that allow for measurements of cell firing and DA release for the natural reward that predicts access to the drug of abuse as well as for the drug reward itself. These studies will shed light on the neural substrate of reward comparison. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]